DNase I targeted degradation of neutrophil extracellular traps to reduce the damage on IgAV rat

Abstract

Background In the past two years, studies have found a significant increase in neutrophil extracellular traps (NETs) in patients with IgA vasculitis (IgAV), which is correlated with the severity of the disease. NETs have been reported as an intervention target in inflammatory and autoimmune diseases. This study aimed to investigate the effect of targeted degradation of NETs using DNase I in IgAV rat model. Methods Twenty-four Sprague-Dawley rats were randomly divided into three groups: the IgAV model group, the DNase I intervention group and the normal control group, with an average of 8 rats in each group. The model group was established by using Indian ink, ovalbumin, and Freund’s complete adjuvant. In the intervention group, DNase I was injected through tail vein 3 days before the end of established model. The circulating cell free-DNA (cf-DNA) and myeloperoxidase-DNA (MPO-DNA) were analyzed. The presence of NETs in the kidney, gastric antrum and descending duodenum were detected using multiple fluorescences immunohistochemistry and Western blots. Morphological changes of the tissues were observed. Results After the intervention of DNase I, there was a significant reduction in cf-DNA and MPO-DNA levels in the intervention group compared to the IgAV model group (all P<0.001). The presence of NETs in renal, gastric, and duodenal tissues of the intervention group exhibited a significant decrease compared to the IgAV model group (P < 0.01). Moreover, the intervention group demonstrated significantly lower levels of renal MPO and citrullinated histone H3 (citH3) protein expression when compared to the IgAV model group (all P < 0.05). The HE staining results of intervention group demonstrated a significant reduction in congestion within glomerular and interstitial capillaries. Moreover, there was a notable improvement in gastric and intestinal mucosa necrosis, congestion and bleeding. Additionally, there was a substantial decrease in inflammatory cells infiltration. Conclusion The degradation of NETs can be targeted by DNase I to mitigate tissue damage in IgAV rat models. Targeted regulation of NETs holds potential as a therapeutic approach for IgAV.

Inhibiting Neutrophil Extracellular Traps Protects against Ultraviolet B-Induced Skin Damage: Effects of Hochu-ekki-to and DNase I

“…DNase I effectively degrades the DNA backbone and has been used to treat inflammatory diseases in vivo [22][23][24][25][26][27]. As a constituent of the host defense system, DNase I effectively degrades the DNA backbone within NETs, making it a potential therapeutic target for NETs [22][23][24][25][26][27]. This study illustrates the direct degradation of NET components by DNase I following UV-B irradiation.…”

“…Studies have evidenced the direct targeting effect of DNase I on NET degradation [22][23][24][25][26][27]. DNase I effectively degrades the DNA backbone and has been used to treat inflammatory diseases in vivo [22][23][24][25][26][27].…”

“…Studies have evidenced the direct targeting effect of DNase I on NET degradation [22][23][24][25][26][27]. DNase I effectively degrades the DNA backbone and has been used to treat inflammatory diseases in vivo [22][23][24][25][26][27]. As a constituent of the host defense system, DNase I effectively degrades the DNA backbone within NETs, making it a potential therapeutic target for NETs [22][23][24][25][26][27].…”